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Blunted nitric oxide-mediated inhibition of sympathetic nerve activity within the paraventricular nucleus in diabetic rats.
Am J Physiol Regul Integr Comp Physiol. 2006 Apr; 290(4):R992-R1002.AJ

Abstract

Recent evidence suggests that a central mechanism may be contributing to the sympathetic abnormality in diabetes. Nitric oxide (NO) has been known as a neurotransmitter in the central nervous system. The goal of this study was to examine the role of the endogenous NO system of the paraventricular nucleus (PVN) in regulation of renal sympathetic nerve activity (RSNA) in streptozotocin (STZ)-induced diabetic rats. The change in number of NADPH-diaphorase-positive neurons [a marker for neuronal NO synthase (nNOS) activity] in the PVN was measured. Diabetic rats were found to have significantly fewer nNOS positive cells in the PVN than in the control group (120 +/- 11 vs. 149 +/- 13, P < 0.05). Using RT PCR, Western blotting and immunofluorescent staining, it was also found that nNOS mRNA expression and protein level in the PVN were significantly decreased in the diabetic rats. Furthermore, using an in vivo microdialysis technique, we found that there was a lower NO(x) release from the PVN perfusates in rats with diabetes compared with the control rats (142 +/- 33 nM vs. 228 +/- 29 nM, P < 0.05). In alpha-chloralose- and urethane-anesthetized rats, an inhibitor of NO synthase, l-NMMA, microinjected into the PVN produced a dose-dependent increase in RSNA, mean arterial pressure (MAP), and heart rate (HR) in both control and diabetic rats. These responses were significantly attenuated in rats with diabetes compared with control rats (RSNA: 11 +/- 3% vs. 35 +/- 3%, P < 0.05). On the other hand, an NO donor, sodium nitroprusside (SNP), microinjected into the PVN produced a dose-dependent decrease in RSNA, MAP, and HR in the control and diabetic rats. RSNA (17 +/- 3%, vs. 41 +/- 6%, P < 0.05) and MAP in response to SNP were significantly blunted in the diabetic group compared with the control group. In conclusion, these data indicate an altered NO mechanism in the PVN of diabetic rats. This altered mechanism may contribute to the increased renal sympathetic neural activity observed in diabetes.

Authors+Show Affiliations

Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 985850 Nebraska Medical Center, Omaha, NE 68198-5850, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16322352

Citation

Zheng, Hong, et al. "Blunted Nitric Oxide-mediated Inhibition of Sympathetic Nerve Activity Within the Paraventricular Nucleus in Diabetic Rats." American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 290, no. 4, 2006, pp. R992-R1002.
Zheng H, Mayhan WG, Bidasee KR, et al. Blunted nitric oxide-mediated inhibition of sympathetic nerve activity within the paraventricular nucleus in diabetic rats. Am J Physiol Regul Integr Comp Physiol. 2006;290(4):R992-R1002.
Zheng, H., Mayhan, W. G., Bidasee, K. R., & Patel, K. P. (2006). Blunted nitric oxide-mediated inhibition of sympathetic nerve activity within the paraventricular nucleus in diabetic rats. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 290(4), R992-R1002.
Zheng H, et al. Blunted Nitric Oxide-mediated Inhibition of Sympathetic Nerve Activity Within the Paraventricular Nucleus in Diabetic Rats. Am J Physiol Regul Integr Comp Physiol. 2006;290(4):R992-R1002. PubMed PMID: 16322352.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blunted nitric oxide-mediated inhibition of sympathetic nerve activity within the paraventricular nucleus in diabetic rats. AU - Zheng,Hong, AU - Mayhan,William G, AU - Bidasee,Keshore R, AU - Patel,Kaushik P, Y1 - 2005/12/01/ PY - 2005/12/3/pubmed PY - 2006/6/10/medline PY - 2005/12/3/entrez SP - R992 EP - R1002 JF - American journal of physiology. Regulatory, integrative and comparative physiology JO - Am J Physiol Regul Integr Comp Physiol VL - 290 IS - 4 N2 - Recent evidence suggests that a central mechanism may be contributing to the sympathetic abnormality in diabetes. Nitric oxide (NO) has been known as a neurotransmitter in the central nervous system. The goal of this study was to examine the role of the endogenous NO system of the paraventricular nucleus (PVN) in regulation of renal sympathetic nerve activity (RSNA) in streptozotocin (STZ)-induced diabetic rats. The change in number of NADPH-diaphorase-positive neurons [a marker for neuronal NO synthase (nNOS) activity] in the PVN was measured. Diabetic rats were found to have significantly fewer nNOS positive cells in the PVN than in the control group (120 +/- 11 vs. 149 +/- 13, P < 0.05). Using RT PCR, Western blotting and immunofluorescent staining, it was also found that nNOS mRNA expression and protein level in the PVN were significantly decreased in the diabetic rats. Furthermore, using an in vivo microdialysis technique, we found that there was a lower NO(x) release from the PVN perfusates in rats with diabetes compared with the control rats (142 +/- 33 nM vs. 228 +/- 29 nM, P < 0.05). In alpha-chloralose- and urethane-anesthetized rats, an inhibitor of NO synthase, l-NMMA, microinjected into the PVN produced a dose-dependent increase in RSNA, mean arterial pressure (MAP), and heart rate (HR) in both control and diabetic rats. These responses were significantly attenuated in rats with diabetes compared with control rats (RSNA: 11 +/- 3% vs. 35 +/- 3%, P < 0.05). On the other hand, an NO donor, sodium nitroprusside (SNP), microinjected into the PVN produced a dose-dependent decrease in RSNA, MAP, and HR in the control and diabetic rats. RSNA (17 +/- 3%, vs. 41 +/- 6%, P < 0.05) and MAP in response to SNP were significantly blunted in the diabetic group compared with the control group. In conclusion, these data indicate an altered NO mechanism in the PVN of diabetic rats. This altered mechanism may contribute to the increased renal sympathetic neural activity observed in diabetes. SN - 0363-6119 UR - https://www.unboundmedicine.com/medline/citation/16322352/Blunted_nitric_oxide_mediated_inhibition_of_sympathetic_nerve_activity_within_the_paraventricular_nucleus_in_diabetic_rats_ L2 - https://journals.physiology.org/doi/10.1152/ajpregu.00363.2005?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -